Antiviral innate immune response in non-myeloid cells is augmented by chloride ions via an increase in intracellular hypochlorous acid levels

Sci Rep. 2018 Sep 11;8(1):13630. doi: 10.1038/s41598-018-31936-y.

Abstract

Phagocytes destroy ingested microbes by producing hypochlorous acid (HOCl) from chloride ions (Cl-) and hydrogen peroxide within phagolysosomes, using the enzyme myeloperoxidase. HOCl, the active ingredient in bleach, has antibacterial/antiviral properties. As myeloperoxidase is needed for HOCl production, non-myeloid cells are considered incapable of producing HOCl. Here, we show that epithelial, fibroblast and hepatic cells have enhanced antiviral activity in the presence of increasing concentrations of sodium chloride (NaCl). Replication of enveloped/non-enveloped, DNA (herpes simplex virus-1, murine gammaherpesvirus 68) and RNA (respiratory syncytial virus, influenza A virus, human coronavirus 229E, coxsackievirus B3) viruses are inhibited in a dose-dependent manner. Whilst treatment with sodium channel inhibitors did not prevent NaCl-mediated virus inhibition, a chloride channel inhibitor reversed inhibition by NaCl, suggesting intracellular chloride is required for antiviral activity. Inhibition is also reversed in the presence of 4-aminobenzoic hydrazide, a myeloperoxidase inhibitor, suggesting epithelial cells have a peroxidase to convert Cl- to HOCl. A significant increase in intracellular HOCl production is seen early in infection. These data suggest that non-myeloid cells possess an innate antiviral mechanism dependent on the availability of Cl- to produce HOCl. Antiviral activity against a broad range of viral infections can be augmented by increasing availability of NaCl.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Aniline Compounds / pharmacology
  • Animals
  • Chloride Channels / antagonists & inhibitors
  • Chloride Channels / immunology
  • HeLa Cells
  • Humans
  • Hydrogen Peroxide / immunology*
  • Hypochlorous Acid / immunology*
  • Immunity, Innate*
  • Ions
  • Mice
  • NIH 3T3 Cells
  • Peroxidase / antagonists & inhibitors
  • Peroxidase / immunology
  • Sodium Chloride / immunology*
  • Viruses / immunology*

Substances

  • Aniline Compounds
  • Chloride Channels
  • Ions
  • Sodium Chloride
  • 4-aminobenzhydrazide
  • Hypochlorous Acid
  • Hydrogen Peroxide
  • MPO protein, human
  • Peroxidase